NIH Grant Abstracts

National Institutes of Health Grant Abstracts

NIH Principal Investigators at Legacy:

R01NS084920 "Glycine augmentation therapy for the treatment of epilepsy"

In this clinically oriented research proposal a combination of mechanistic and therapeutic studies will allow us to determine whether therapeutic glycine augmentation might be a novel pharmacological principle for the treatment of seizures in temporal lobe epilepsy. We will make novel and innovative use of glycine augmenting drugs that have already been tested in clinical trials (phase II/III) to treat cognitive symptoms in schizophrenia. Identification and characterization of a novel anticonvulsant role of existing drugs will open new opportunities for efficient seizure control combined with pro-cognitive properties.

The principal goal of this proposal is to identify important molecular and cellular components of optic nerve head (ONH) connective tissue and retrolaminar myelin remodeling in monkey early experimental glaucoma (EG). To do so we will employ: state of the art quantitative mass spectroscopy, quantitative ONH immunohistochemistry and electron microscopy, and precise anatomic colocalization of all microscopic findings to in vivo optical coherence tomography (OCT). All outcomes will be reported in anatomically consistent, 30 degree ONH sectors that are oriented relative to the axis between the fovea and Bruch’s membrane opening. The results of these studies will allow us to identify age-related differences in connective tissue and myelin remodeling in monkey early EG and provide unprecedented microscopic support for their early, in vivo, detection by OCT. New hypotheses regarding the contributions of connective tissue and myelin remodeling to retinal ganglion cell injury in early glaucoma, based on these results, will be tested in future research.

R01EY021281 "Optic nerve head SDOCT imaging in glaucoma"

The principal goal of this study is to construct a Spectral Domain Optical Coherence Tomography (SDOCT) phenotyping strategy for the optic nerve head (ONH), peripapillary retinal nerve fiber layer (RNFL) and macula tissues that improves the detection of glaucomatous damage and its progression. Aims 1 and 2 use SDOCT phenotyping to characterize age-related and glaucomatous structural change in monkeys so as to improve their clinical detection in humans (Aims 3 and 4). Expected outcomes include: improved detection of glaucoma onset and progression; confirmation that SDOCT ONH onset and progression predict subsequent RNFL and macula thickness loss; abandonment of clinician cup/disc ratio as the gold standard for clinical disc examination and its replacement with SDOCT anatomy and geometry; and adoption of SDOCT phenotyping by all subspecialties of Ophthalmology and Neurology that image the ONH, RNFL and macula tissues.

R01EY019939 "The role of retinal astrocytes in dynamic blood flow autoregulation"

This project will establish a novel role for astrocytes in maintaining hemodynamic homeostasis in the retina and ONH. We believe that this is mechanism of hemodynamic control that exists in both eye and brain. The outcome will also generate hypotheses for future studies of novel therapeutic targets in diseases associated with autoregulation dysfunction, including glaucoma.